Sensitization of amphetamine-induced stereotyped behaviors during the acute response: Role of D-1 and D-2 dopamine receptors

During the response to an injection of-amphetamine, rapid changes occur in the ability of the drug to induce stereotyped behaviors. This enhanced resp onsivity does not involve changes in the caudate-putamen or nucleus accumbe ns extracellular dopamine response, but appears to require activation of do pamine receptors. In the present studies we examined the role that D-1 and D-2 dopamine receptors might play in the development and expression of the enhanced stereotypy response. In one series of experiments we used the dopa mine agonists, SKF 82958 and quinpirole as relatively selective probes at D -1 and D-2 dopamine receptors, respectively, to test for changes in dopamin e receptor sensitivity following a pretreatment ('priming') with 4.0 mg/kg amphetamine. Doses of both SKF 82958 and quinpirole which were sub-threshol d to induce perseverative behaviors in control animals, promoted stereotype d behaviors in amphetamine-primed animals, suggesting an enhanced sensitivi ty of both D-1 and D-2 receptors. In a second series of experiments, we sou ght to determine whether priming with these relatively selective dopamine r eceptor agonists, as well as the mixed D-1/D-2 agonist, apomorphine, would result in an enhanced stereotypy response to the subsequent administration of non-stereotypy producing doses of amphetamine (0.5-1.5 mg/kg). Priming w ith the dopamine receptor agonists each resulted in an enhanced amphetamine -induced stereotypy response. These results indicate that both D-1 and D-2 dopamine receptors contribute to both the development and the expression of the altered stereotypy responsivity, though several dose- and time-related observations suggest that other mechanisms likely contribute as well. Beca use these changes are apparent during the amphetamine response, they may ha ve important implications for the evolving behavioral alterations which res ult when stimulants are administered in a binge pattern of drug abuse. (C) 1999 Elsevier Science B.V. All rights reserved.